Rab15, a member of the Rab family of small G proteins, is a key regulator in membrane traffic. It was originally identified as a brain-specific protein and is involved in the endocytic recycling pathway [1,3,4]. Rab15 has been associated with processes like endocytosis, and its misregulation may contribute to certain cancers [1]. Genetic models can be valuable for studying its function in various biological contexts.

In neuroblastoma, Rab15 alternative splicing generates multiple isoforms, and the balance of these isoforms, measured by the Rab15(CN)/Rab15(AN1 + AN2+AN3) ratio, is significantly decreased in tumor-initiating cell (TIC) spheres compared to parental cells. This suggests that Rab15 alternative splicing may serve as a biomarker to distinguish TICs from non-TICs in neuroblastoma [1]. In Ehrlichia chaffeensis infection, the bacterium's T4SS effector Etf-3 induces RAB15 upregulation in host cells. RAB15 localizes on E. chaffeensis-containing vesicles (ECVs), inhibits ECV fusion with lysosomes, and induces autophagy. Silencing RAB15 enhances ECV maturation to late endosomes and fusion with lysosomes, as well as inhibits host cell autophagy [2].

In conclusion, Rab15 is crucial for membrane-trafficking-related processes. Model-based research has revealed its significance in neuroblastoma, potentially as a biomarker, and in the pathogenesis of Ehrlichia chaffeensis infection. Understanding Rab15 can provide insights into the mechanisms of these diseases and potentially lead to new therapeutic strategies.